Anti-neuroinflammatory effects of epivernodalol, a sesquiterpene from Vernonia anthelmintica (L.) Willd., in lipopolysaccharide-stimulated murine microglial cells.

Four terpenes-epivernodalol [Epl], cynaropicrin, vernonilide A, and vernodalin-were isolated from Vernonia anthelmintica (L.) Willd., and their effects on interleukin (IL)-6 secretion in lipopolysaccharide (LPS)-stimulated murine BV2 microglial cells were evaluated. To elucidate the underlying mechanisms of their immunomodulatory activity, we quantified the mRNA levels of key cytokines (IL-1β, TNF-α, IL-6, IL-10, and TGF-β) and the expression of CD206 using qRT-PCR. Additionally, surface markers of BV2 cells were analyzed via flow cytometry. Furthermore, we assessed the phosphorylation of NF-κB and its inhibitory protein, IκB, in BV2 microglial cells by western blotting. Our findings demonstrated that Epl exerts anti-neuroinflammatory effects by suppressing NF-κB pathway activation and pro-inflammatory cytokine secretion while enhancing anti-inflammatory cytokines production and promoting M2 polarizations. This study not only reveals a previously unrecognized role of Epl but also provides insights into the identification of novel therapeutic targets for neuroinflammatory diseases.